The objectives of the proposed studies are to elucidate the role of polymorphonuclear leukocytes (PMN) in oral health and disease. PMN appear to play a central role in oral defense mechanisms, and PMN dysfunction is associated with periodontal diseases. However, these cells are also a potential source, of cytokines, such as interleukin 1 beta (IL-1 ) and tumor necrosis factor alpha (TNF ), which are not only of immunological significance but also stimulate bone resorption. It is therefore possible that PMN activity may itself contribute to periodontal pathology. The specific aims of this project are designed to address the hypothesis that the functional state of oral PMN will be reflected by their activity at the level of gene expression, and that this will correlate with the state of health of the periodontium. These aims will be achieved by examining the accumulation and translation of messenger RNA for IL-1 and TNF in salivary and peripheral blood PMN derived from patients with chronic adult periodontitis and from healthy volunteers. In addition, gingival crevicular PMN from diseased sites will be compared with those from healthy sites in selected patients with adult periodontitis. The specific mRNA will be examined by Northern hybridization studies using biotin-labeled DNA probes in resting cells and PMN activated in vitro by exposure to recombinant human granulocyte-macrophage colony stimulating factor. Cytokine production will be measured by ELISA methodology. Results will be correlated with periodontal disease severity, and compared not only with data derived from normal volunteers but also with those of patients following successful treatment of periodontitis.